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AMEDCHEM [email protected] +862168061059 CHINA

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Background Information of JTT-851

JTT-851 is a GPR40 partial agonist. GPR40, also known as FFAR1, belongs to the class A family of G-protein coupled receptors, and is expressed predominantly in pancreatic β cells and enteroendocrine cells.GPR40 partial agonism is a promising new mechanism for the treatment of type 2 diabetes mellitus with clinical proof of concept. 

Solubility of JTT-851

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Mechanism and Indications

Signaling Pathways GPCR/G Protein
Target GPR40
Research Area Metabolic Disease

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase

Chemical Information

M.Wt Formula CAS No. Synonyms
352.47 C23H28O3

Structure Information of JTT-851

Smiles C1CCC2(CC(COC3C=CC([[email protected]](C(O)=O)C#CC)=CC=3)=CCC2)CC1 |&1:12|
InChI InChI=1S/C23H28O3/c1-2-7-21(22(24)25)19-9-11-20(12-10-19)26-17-18-8-6-15-23(16-18)13-4-3-5-14-23/h8-12,21H,3-6,13-17H2,1H3,(H,24,25)/t21-/m1/s1

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GPR40 Activator 1 1309435-60-6 C31H31NO3S 6
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DC260126 346692-04-4 C32H31N5O 7
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MK-2305 905723-46-8 C19H13ClF3NO4S 0
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Chemical and Physical Properties

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[1].Huang H, et al. Discovery of novel benzo[b]thiophene tetrazoles as non-carboxylate GPR40 agonists. Bioorg Med Chem Lett. 2017 Dec 12. pii: S0960-894X(17)31182-4.
GPR40 partial agonism is a promising new mechanism for the treatment of type 2 diabetes mellitus with clinical proof of concept. Most of the GPR40 agonists in the literature have a carboxylic acid functional group, which may pose a risk for idiosyncratic drug toxicity. A novel series of GPR40 agonists containing a tetrazole as a carboxylic acid bioisostere was identified. This series of compounds features a benzo[b]thiophene as the center ring, which is prone to oxidation during phase 1 metabolism. Following SAR optimization targeting GPR40 agonist activity and intrinsic clearance in microsomes (human and rat), potent and metabolically stable compounds were selected for in vivo evaluation. The compounds are efficacious at lowering blood glucose in a SD rat oGTT model.

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